Erythropoietin (Epo) is a primary regulator of erythropoiesis and functions by binding to the receptor (EpoR) on the surface of hematopoietic progenitor cells, followed by receptor-mediated endocytosis of the Epo molecule. We have previously cloned and sequenced the human EpoR gene making it possible for us to examine the tissue and developmental specificity of gene expression in normal and transgenic mice. After generating several lines of transgenic mice expression the EpoR, hematological parameters were measured in transgenic mice and tissue expression was determined in both normal and transgenic from different lines. Our results show that hematological parameters were within normal limits except for a suggestion of increased reticulocyte levels. Human EpoR transcripts were detected in erythroid tissues (bone marrow and spleen) and in the adult brain of transgenic mice. Based on the above discovery, we further examined developmental specificity of EpoR gene in mice. In normal mice, mouse EpoR transcripts in fetal liver were detected at 12 days and decreased with age, disappearing before birth. Endogenous transcripts were also detected in fetal brain. The transcripts at different developmental steps were quantized by competitive PCR. We found that EpoR mRNA was exponentially down-regulated upon development in fetal liver. In transgenic mice, copy number was detected by competitive PCR and tissue expression of the human transgene, was copy number dependent.